rs119463993

chr9-105619962-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001079802.2(FKTN):c.1073A>C(p.Gln358Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FKTN NM_001079802.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.88

Genes affected

FKTN (HGNC:3622): (fukutin) The protein encoded by this gene is a putative transmembrane protein that is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of alpha-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. Defects in this gene are a cause of Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-105619962-A-C is Pathogenic according to our data. Variant chr9-105619962-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 3209.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-105619962-A-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKTN	NM_001079802.2	c.1073A>C	p.Gln358Pro	missense_variant	10/11	ENST00000357998.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKTN	ENST00000357998.10	c.1073A>C	p.Gln358Pro	missense_variant	10/11	5	NM_001079802.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dilated cardiomyopathy 1X Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
Cadd	Uncertain	23
Dann	Uncertain	0.98
DEOGEN2	Benign	0.33	T;T;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.9	L;L;L;L
MutationTaster	Benign	0.99	A;A;A
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.040	B;B;.;.
Vest4		0.55
MutPred		0.57		Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);
MVP		0.91
MPC		0.12
ClinPred		0.73	D
GERP RS		6.1
Varity_R		0.40
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs119463993; hg19: chr9-108382243;